No abstract

In anaesthetized cats, a biphasic contraction of the urinary bladder, consisting of an initial spike followed by a longer-lasting contracture, was elicited by 5-hydroxytryptamine (5-HT) in doses of 3-30 micrograms/kg, i.a. Administration of MDL 72222 (30, 100 and 300 micrograms/kg, i.v.), which specifically antagonizes the M-type 5-HT receptors, selectively blocked the spike phase of the 5-HT response. Ketanserin (30, 100 and 300 micrograms/kg, i.v.), on the other hand, eliminated only the second phase of the 5-HT-induced bladder contraction. Injection of MDL 72222 (300 micrograms/kg) after ketanserin (300 micrograms/kg), or of 100 micrograms/kg of methysergide or cyproheptadine, or 300 micrograms/kg of ketanserin after MDL 72222 (300 micrograms/kg), led to blockade of both phases of the response to 5-HT. The contractile response to dimethylphenylpiperazinium (DMPP) remained unaffected. These results clearly show that the early and late phases of the cat urinary bladder contraction elicited by 5-HT are mediated by M and 5-HT2 receptors, respectively.

Internal and external carotid blood flows in anesthetized monkeys were measured simultaneously using electromagnetic flowmeters. Complete dose-response relationships were established for the effects of intracarotid infusion of several humoral agents implicated in migraine. Both the internal and external carotid vasculatures were constricted by serotonin and prostaglandin F2alpha and dilated by bradykinin, histamine, and acetylcholine. Noradrenalin and adrenaline constricted the external carotid vasculature but had little direct effect in the internal carotid territory. Prostaglandin E1 dilated the external carotid vasculature. Low doses of prostaglandin E1 produced dilation in the internal carotid circulation, but with higher doses there was a paradoxical abolition of this effect.

1 Previous investigations into the vascular actions of biogenic amines implicated in migraine have shown that the contractile effects of both 5-hydroxytryptamine (5-HT) and noradrenaline (NA) in the rabbit ear artery are mediated by a direct sympathomimetic action at a-adrenoceptors, while in the rabbit aorta, 5-HT and NA act on pharmacologically distinct receptors. The purpose of the present investigation was to determine whether the absence of 5-HT receptors in rabbit ear arteries is characteristic of distributing arteries in general, or is confined to particular regional circulations. 2 Agonist-antagonist interactions were studied in various rabbit vascular preparations (common carotid, external carotid and femoral arterial strips, and perfused ear arteries) by determining pA2 values for pizotifen and phentolamine against 5-HT-and NA-induced contractile responses.3 In common carotid and femoral arteries, pizotifen was a potent competitive antagonist of 5-HT, but weak against NA. The converse applied to phentolamine. In external carotid and ear arteries, pizotifen was a weak competitive antagonist of both 5-HT and NA, whereas phentolamine was a potent competitive antagonist of both. Cocaine did not influence pA2 values against NA. 4 5-HT and NA were of similar potency in common carotid and femoral arteries, but 5-HT was much less potent than NA in external carotid and ear arteries. 5 The results indicate that rabbit common carotid and femoral arteries contain both D-type 5-HT receptors and a-adrenoceptors, as does the aorta. However, external carotid arteries, like ear arteries, do not contain specific 5-HT receptors. The action of 5-HT in the external carotid artery is mediated by a-adrenoceptors; this is a direct sympathomimetic action since it was not inhibited by cocaine or reserpine-pretreatment. 6 The absence of 5-HT receptors in the rabbit extracranial circulation may limit the usefulness of this species as a model for research relating to migraine.